Hypoxic-ischemic encephalopathy remains the main neurological complication in the newborn. The long range purpose of this investigation is to discover new therapies to prevent brain damage due to birth asphyxia and its devastating sequelae. The specific aims of this study are: (1) To assess the neuroprotective effects of either postischemic mild hypothermia or adenosine potentiation in the neonatal rat pup (2). To assess the combined neuroprotective effects of postischemic mild hypothermia and adenosine potentiation in the neonatal rat pup. It is hypothesized that both hypothermia and Ado agents individually will be neuroprotective and in combination will have an even greater benefit, as measured by comparative hemispheric brain weights, infarct size, alterations in neuronal morphology scores and glutamate levels, using light microscopy, immunohistochemistry and neurochemistry microdialysis as appropriate. The animal model will be 21 litters (10-12 pups/litter) of 7 d old Sprague-Dawley rat pups, exposed to the Rice Vannucci model for hypoxic-ischemic insult and various combinations of recovery conditions with hypothermia and adenosine (Ado) potentiating agents. This research hopes to shed light on a crucial clinical question, regarding the relationship of thermal management, adenosine potentiation and neuroprotection.